Closing the Gaps on Medical Education in Low-Income Countries Through Information & Communication Technologies: The Mozambique Experience.
Medical training in developing countries has continuously faced challenges to produce the needed number of cadres and maintain the needed quality standards. Mozambique, a low-income country in Southern Africa, has a major disparity in distribution of medical doctors in the country and only a small proportion are trained as specialists and/or retained as faculty. In this context, we thought that Information and Communication Technologies (ICT) are an attractive tool to support expansion of medical training and residency programs and designed a strategy for its use to promote changes in the learning environment of a university teaching hospital in this country. Beginning in 2010-under the Medical Education Partnership Initiative between Universidad Eduardo Mondlane, Mozambique, and University of California San Diego, United States of America - we conducted extensive interviews to 21 UEM faculty and medical trainees to assess barriers to education and medical care at the major referral hospital in Mozambique. Then, changes were made to address the issues raised mainly through building an ICT infrastructure to improve connectivity, improving access to medical information, distributing communication and mobile medical devices, as well as fostering exchange between students, residents and faculty members. These changes were tracked years after to evaluate adoption. Internet access with large bandwidth and devices such as tablets and computers were distributed to increase access to medical information. The students: resident ratio improved from 13:1 to 5:1 at the end of the project. Additional 25 new faculty members were involved in clinical training, mainly through incentives such as faculty development courses and research training. Teleconferences and other exchanges using ICT have evolved from being used as a platform for weekly clinical rounds and case discussions, to become a day-to-day tool for implementation of quality improvement processes and research projects. New exchange programs between local and foreign institutions were fostered to create a growing network with over 20 institutions at the end of the program. Importantly, these changes persisted beyond the project, and constituted a driver for transformative education and distance learning. Context-tailored use of ICT and mobile medical devices transformed medical education by improving the learning environment, addressing scarcity and low quality of trained doctors in a low-income setting of Africa. This strategy has the potential to reduce health disparities and contribute to achieving universal health coverage. Efforts to guaranty sustainability and health professional's retention are warranted.


The effect of sound speed profile on shallow water shipping sound maps.
Sound mapping over large areas can be computationally expensive because of the large number of sources and large source-receiver separations involved. In order to facilitate computation, a simplifying assumption sometimes made is to neglect the sound speed gradient in shallow water. The accuracy of this assumption is investigated for ship generated sound in the Dutch North Sea, for realistic ship and wind distributions. Sound maps are generated for zero, negative and positive gradients for selected frequency bands (56 Hz to 3.6 kHz). The effect of sound speed profile for the decidecade centred at 125 Hz is less than 1.7 dB.


Interpretive reporting of laboratory data: proposed criteria to qualify as a high-quality, limited clinical pathology consultation.
To present recommended criteria designed to improve the computer-based interpretation of laboratory test results. Guidelines for providing high-quality test interpretations and an outline for incorporating such criteria into a program for interpretive reporting are presented. Traditionally, when a laboratory reports a test result, the clinician interprets it within the clinical context. More recently, even in the absence of clinical information about the patient, laboratories that report test results, including biochemical thyroid function tests, have begun to insert "informative" statements about the test. These statements fail to provide an adequate limited pathology consultation that merits the CPT code 80500. Such interpretations can be improved by making them optional, specific for the test result, considerations rather than recommendations, and accompanied, on request, by an expanded list of differential diagnoses and an itemization of drugs known to affect the test result. High-quality interpretations of laboratory tests should improve patient care, avoid unnecessary costs, and prompt appropriate referrals to specialists.


The prognostic values of prognostic nutritional index in extensive-stage small-cell lung cancer.
We aimed to assess the prognostic and predictive significance of pretreatment Prognostic Nutritional Index (PNI) in extensive-stage small-cell lung cancer (ES-SCLC) patients treated with first-line chemotherapy. We designed this study to evaluate the prognostic role of PNI in 147 ES-SCLC patients treated with platinum-based combination regimen between 2011 and 2018. Kaplan-Meier survival analyses and Cox proportional hazard models were used to examine the effects of basal PNI on overall survival (OS). The median age of the patients was 61 (range 38-81). The cutoff value for PNI was determined for whole group and patients were dichotomized into high (≥49.17) and low (<49.17). Seventy-eight (53.1%) patients had low PNI score and 69 (46.9%) patients had high PNI score. Patients with the high PNI score had better OS than those with low PNI (13 versus 12 months, respectively, and P = 0.03). The relationship between PNI score and OS was more prominent in patients over 65 years of age (13 versus 10 months, respectively, and P = 0.03). Progression-free survival of patients with complete response to first-line treatment was statistically significantly better than the other patients (8 versus 7 months, respectively, and P = 0.02). Similarly, OS was statistically significantly better than the other patients (15 versus 8 months, respectively, and P = 0.001). The results of our study show that PNI score is useful in evaluating the OS of patients with ES-SCLC. PNI is a cost-effective prognostic marker and should therefore be included in routine clinical practice.


Improved collagen bilayer dressing for the controlled release of drugs.
A novel bilayer dressing has been developed from bovine succinylated collagen. The dressing contains an antibiotic, Ciprofloxacin, for both immediate and time-regulated release for controlling the infection, as the infected open wounds need special care. The dressing consists of a sponge and a film, both prepared from succinylated bovine collagen. The sponge has a smooth surface on one side; its rough surface on the other side forms the bilayer system with the film. Both sponge and film act as an anionic reservoir to hold the cationic Ciprofloxacin. The drug, after dispersing in poly (N-vinyl-2-pyrrolidione) (PVP) solution is allowed to spread in the bilayer system by diffusion. The drug stays in the bilayer system because of ionic binding, but starts releasing when comes in contact with the wound. Release of the drug is immediate, but it is regulated by ionic binding between the drug and succinylated collagen. The wound exudates, and there is a polarity-controlled release of the drug from the bilayer system. The PVP and bilayer system permits only time-regulated release, and the system lasts up to 5 days with therapeutically sufficient drug availability.


A Comparison of Residents' Knowledge Regarding the Surviving Sepsis Campaign 2012 Guideline.
Recently, Surviving Sepsis Campaign (SSC) guideline was updated. Our objective was to evaluate the knowledge of residents in different departments regarding the SSC 2012. A cross-sectional, descriptive self-questionnaire was distributed to interns and residents in the Departments of Internal Medicine, Surgery, and Emergency Medicine. The response rate was 136 (89%) from 153 residents. The residents included 46 (33%) interns, 42 (31%) internal medicine residents, 41 (30%) surgical residents, and 7 (5%) emergency residents. Regarding the definitions of severe sepsis and septic shock, only 44 (32.4%) residents were able to differentiate the severity of sepsis. The surgical residents had a significantly lower rate of correct answers than that of internal medicine residents (12.2% vs. 45.2, P = 0.001), emergency residents (12.2% vs. 57.1%, P = 0.005), and interns (12.2% vs. 34.8%, P = 0.014). Only 77 (51.5%) residents would measure blood lactate in patients with sepsis. In respect to the dose of fluid resuscitation, only 72 (52.9%) residents gave the recommended fluid (30 ml/kg) within the first 3 h. Surgical residents had a significantly lesser percentage of correct answers than that of internal medicine residents (29.3% vs. 69%, P < 0.0001) and interns (29.3% vs. 60.8%, P = 0.003). About 123 (90.4%) and 115 (84.6%) residents knew the appropriate targets for mean arterial pressure and vasopressors, respectively. Most residents could give antimicrobial drugs (73.5%) and steroids (93.4%) appropriately in the treatment of patients with septic shock. However, only half of the residents knew the target range of blood sugar control in patients with sepsis. Our residents' knowledge about the SSC 2012 is not satisfactory. Further instruction concerning sepsis management is required.


Phenotypic and genotypic characteristics of Streptococcus porcinus isolated from human sources.
The phenotypic and genotypic characteristics of 25 Streptococcus porcinus isolates recovered from human sources were investigated and compared to the characteristics of 17 reference strains obtained from nonhuman sources. All of the S. porcinus isolates were beta-hemolytic (wide zones), susceptible to vancomycin, gave positive results for the leucine aminopeptidase and l-pyrrolidonylarylamidase tests, and produced acids from mannitol and sorbitol. Most of them were positive for the CAMP test and resistant to bacitracin. The isolates were susceptible to most of the 14 antimicrobials tested, except for tetracycline, for which 80% of the human isolates and 35.2% of the nonhuman strains were resistant. The tet(M) and the tet(O) genes were detected in 23 (88.5%) and 8 (30.8%) of the 26 tetracycline-resistant isolates, respectively. Analysis of whole-cell protein profiles obtained after sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a high similarity among the profiles. Chromosomal DNA was analyzed by pulsed-field gel electrophoresis (PFGE) after digestion with SmaI and by random(ly) amplified polymorphic DNA (RAPD)-PCR using primer 1254. Analysis of SmaI-restricted genomic DNA revealed the substantial genetic diversity among S. porcinus isolates from nonhuman sources, which were also serologically more diverse. Most of the human isolates belonged to serogroup NG1 and shared highly related PFGE profiles that were distinct from profiles of isolates from nonhuman sources. These results were in agreement with those obtained by analysis of amplicons after RAPD-PCR, indicating the potential ability of these techniques for typing S. porcinus and suggesting the occurrence of a few clonal groups of S. porcinus strains adapted to the human host.


Equality between age-groups.
The first part of the article considers what proponents of the most familiar egalitarian moral theories would say about age-group inequality. I claim that these theories have intuitively objectionable consequences. The second part explains and criticizes a theory of justice formulated specifically for age-groups: Norman Daniels' prudential lifespan account. In the third part I explain two views that seem to me to give a better account of justice between the young and the old.


[Sports and pregnancy].
MATERNAL ASPECTS: Cardiorespiratory responses to exercise in pregnant women generally don't differ from those in nonpregnant women. Impairment of the cabability of the uteroplacental unit to maintain a sufficient oxygen and substrate supply to the fetus should be avoided by performing exercise in a submaximal range. Increase in body weight, a shift of the center of gravidity, and the ligamentous laxity in pregnancy lead to a certain joint instability and consecutively to an increased risk of injury. Therefore contact sports and sports with a high potential of injury are not suitable in pregnancy. Furthermore the beneficial effects of exercise on glucose metabolism especially in pregnant women with an impaired glusose tolerance, psychological well-being, delivery, and lactation are discussed. Exercise results in an elevation of the fetal heart rate. So far no pathological heart rate alterations could be observed. There are controversial findings concerning the influence of exercise on birth weight. Actually no retardation below the 10th percentile could be demonstrated. To prevent pregnancy complications like preterm labour or placental abruption exercises with a risk of blunt abdominal trauma are not recommended in the 2nd and 3rd trimester. Additionally the effects of exercise on embryogenesis and the possible implications of hyperthermia are presented. In general, pregnant women should practise exercise in a moderate, i. e. submaximal aerobic range. Preexisting cardiopulmonary diseases and pregnancy pathologies have to be considered as contraindications. Thus gestational age adapted exercise represents a safe and effective support for mother and fetus. Recommendations concerning exercise in pregnancy underwent significant changes during the past three decades. Today there is a lot of evidence for the beneficial effects of moderate exercise in pregnancy even in formerly inactive women. This review first presents aspects of maternal and fetal physiology with special respect to exercise in pregnancy. Subsequently, risks and contraindications as well as the suitability of different kinds of exercise for pregnant woman are discussed.


Gastric emptying in hyperthyroidism.
We undertook a prospective study to survey gastric emptying of a solid meal in patients with hyperthyroidism until euthyroidism was reached after pharmacological treatment with thiamazole. Eleven women (aged 33.2 +/- 3.2 SE yr) with recently diagnosed hyperthyroidism participated in the study. Thyroid function parameters and gastric emptying were examined on three occasions, before treatment, during the third week of treatment, and after euthyroidism was restored. The control group was composed of 12 age-matched healthy women (aged 34.5 +/- 2.3 yr). Gastric emptying of a 390-kcal 99mTc-labeled solid meal was continuously recorded under a gamma camera over 90 min. A power-exponential model was used for analysis of the gastric emptying course. Three gastric emptying parameters were computed: t1/2, the gastric half-emptying time, S, the curve shape parameter, and K, the slope of the curve. Pretreatment solid phase gastric emptying of the patients was not statistically significantly different from that of the healthy control subjects: t1/2, 82.8 +/- 4.9 vs 93.5 +/- 6.0 min; S, 0.996 +/- 0.103 vs 1.032 +/- 0.064; and K, 8.42 +/- 0.47 vs 7.64 +/- 0.39 min(-1) x 10(-3). Gastric emptying during the third week of treatment did not change in comparison with pretreatment gastric emptying: t1/2, 84.3 +/- 8.2 min; S, 1.014 +/- 0.123; and K, 8.92 +/- 1.12 min(-1) x 10(-3). On the other hand, a slight increase in rate of gastric emptying was observed after the restoration of euthyroidism (t1/2, 74.6 +/- 5.8 min, and K, 9.65 +/- 0.76 min(-1) x 10(-3), p < 0.05 vs healthy control subjects for both parameters), but no significant change was observed in the shape parameter (S, 0.980 +/- 0.066). In women with hyperthyroidism, gastric emptying of solids does not differ significantly from that observed in age-matched healthy control subjects and remains unaffected during pharmacological treatment. After restoration of euthyroidism, a slight but statistically significant increase in the rate of gastric emptying occurs in patients as compared with healthy control subjects.


Periodontitis in the United States: beyond black and white.
This paper examines whether historical disparities in periodontal status between African Americans and whites in the United States have increased, decreased, or remained the same over the 15-year period between the First National Health and Nutrition Examination Survey (NHANES I, 1971-74) and the Third National Health and Nutrition Examination Survey (NHANES III, 1988-94). This study compared the magnitude of the relative and absolute differences in the periodontal status of African-American and white adults in NHANES I and again in NHANES III. The prevalence of periodontitis in the US adult population in NHANES I was 31.6 percent, with African Americans exhibiting higher prevalence than whites. In NHANES III, using a different case-definition for periodontitis, the overall prevalence was 11.9 percent, with African Americans again exhibiting higher prevalence than whites. The magnitude of the intrasurvey relative and absolute differences between African Americans and whites increased between NHANES I and NHANES III. This finding remained after adjustment in the logistic regression analyses. After adjustment for all covariates in the model, African Americans were more likely to exhibit periodontitis than whites in both NHANES I (odds ratio [OR] = 1.31; 95% confidence intervals [CI] = .78, 2.19) and NHANES III (OR = 2.09; 95% CI = 1.68, 2.60). However, the CI included 1.00 in NHANES I. Disparities in periodontitis between African Americans and whites are pervasive and have increased over time. This increase appears to be driven by social, cultural, and behavioral factors.


Solvent-dependent, low-temperature solution phase synthesis of FePt nanowires.
Preparation of FePt nanowires by thermal decomposition of the solution mixture of equimolar Fe(CO)5 and Pt(acac)2 in n-octylamine will be presented in this account. The nanowires with the average diameter about 2 nm and the length of several hundred nanometers were characterized by TEM, EDS, XRD. It is believed that FePt nanowires were generated via the catalytic solution-liquid-solid (S-L-S) synthetic approach. This process is strongly dependent on the solvent and barely on the reaction temperature and the concentrations of precursors.


Alkaline phosphatase-triggered assembly of etoposide enhances its anticancer effect.
Etoposide is a cancer-targeting drug but an overdose of etoposide leads to immunosuppression in patients. Therefore, the development of a new strategy to enhance its anticancer effect, while in the meantime alleviating its adverse effects, is important but challenging. In this work, with the assistance of a hydrogelator precursor Nap-Phe-Phe-Tyr(H2PO3)-OH (1P), etoposide phosphate (EP) was subjected to alkaline phosphatase (ALP)-triggered assembly, which obviously enhanced its anticancer efficacy in vitro and in vivo. In vitro tests indicated that the assembly of EP with 1P resulted in a slow release of etoposide and long-term inhibitory effects on HeLa cells. In vivo experiments indicated that, compared with those of EP-treated mice, the tumor growth of EP + 1P-treated mice was further inhibited while their body weight loss was alleviated. We envision that our hydrogelator-assisted assembly strategy could be applied to enhance the therapeutic effects of more drugs, while in the meantime alleviating their adverse effects in the future.


[Congestive heart failure--some current problems].
The congestive heart failure (CHF) has become one of the most common syndromes afflicting the population. The long-term prognosis of these patients is bad. The CHF shows a tendency toward fast progressive development. The aim of our study was a retrospective investigation on CHF patients, a determination of CHF functional class by NYHA and its type, a determination of the most important diseases leading to heart decompensation and of the reasons for dead in these patients. For a 6-year period we investigated 6428 patients. 1095 (17.03%) of them were with a different degree of CFH. More of them were with II and III functional class of CHF by NYHA. In the age decade from 61 to 70 years the frequency of CHF increased significantly. The most important diseases leading to CHF syndrome were chronic ischemic disease, arterial hypertension, COPD with chronic cor pulmonale and valve diseases. The average age of deceased CHF patients was 67.8 +/- 7.4 years. After the manifestation of the first group of symptoms the mean life duration of CHF patients was 13.2 +/- 4.1 years.


Quantitative Assessment of Peroneal Artery Pressure at the Ankle With Noninvasive Vascular Testing.
Although the foot and ankle derives its arterial supply from a combination of the anterior tibial artery (ATA), posterior tibial artery (PTA), and peroneal artery (PA), the focus of clinical examination techniques and noninvasive vascular testing is primarily on the ATA and PTA and not on the PA. The objectives of the present investigation were to evaluate the feasibility of incorporating an assessment of the PA into a noninvasive vascular testing protocol and to collect normative data of pressure measurements of the PA at the ankle. We attempted to locate a Doppler signal of the PA posterior to the lateral malleolus in consecutive patients undergoing our institution's standard protocol for lower extremity noninvasive vascular testing using the ankle-brachial index and photoplethysmography. An audible signal of the PA with an available pressure measurement recording posterior to the lateral malleolus was found in a large majority (92.0%) of the studied legs with peripheral arterial disease. We also found pressure measurements in the PA generally equivalent to that of the ATA and PTA. The mean ± standard deviation systolic pressure of the PA was 130.33 ± 44.74 (range 54 to 255) mm Hg, with a corresponding ankle-brachial index of 0.92. The results of the present investigation provide unique information on a potentially underappreciated aspect of lower extremity vascular anatomy with the potential to affect rearfoot surgical decision making and planning.


Wings of the common house fly (Musca domestica L.): importance in mechanical transmission of Vibrio cholerae.
The importance of house fly (Musca domestica L) wings in mechanical transmission of bacteria was studied. A droplet of phosphate-buffered saline containing Vibrio cholerae was rolled along one wing of each house fly. None adhered to the wings but small proportions of the bacterium were isolated from about half the wings. Vibrio cholerae was spread onto the ventral wing surfaces of each unconscious house fly which then was placed inside a bottle. When it regained consciousness, the types of activity it performed over five minutes were noted before the house fly was killed and the bacteria on its wings numerated. Control were house flies killed before inoculation. The proportion of house flies with bacteria on their wings and the mean number of bacteria remaining were significantly less on live house flies than killed controls. Among the live house flies, bacteria were detected on fewer house flies which flew (25%) than those which did not fly (81%). In addition, the mean number of bacteria on the former was significantly less than the latter (5 against 780 colonies). However, both these parameters were not significantly different between the group which performed and the group which did not perform wing grooming; takeoff and alighting over short distances, and somersaulting. Wings of unconscious house flies tethered by their thoraxes were inoculated with V. cholerae. After regaining consciousness, the house flies were allowed to move their wings in flight motions for up to 30 seconds. Small proportions of bacteria remained on all the house flies. House flies were placed in a chamber containing a liquid bait spiked with V. cholerae. After two hours, 10 were removed sequentially and cultured for V. cholerae. The bacterium was isolated from four house flies: two from the legs, and two others from their bodies minus legs and wings. In conclusion, house fly wings do not play an important role in mechanical transmission of bacteria suspended in a non-adhering liquid medium because of the low transfer rate of the bacteria to the wings and poor retention of bacteria on the wings during normal house fly activities.


A systematic study and effect of PLA/Al2O3 nanoscaffolds as dental resins: mechanochemical properties.
One of the major and important challenges in dental composite resin and restoration is the mechanical performance and property of materials. Nanotechnology can produce nanoscale materials that are used in dentistry to help stabilize and strengthen the dentistry. In this work, we study the synthesis and characterization of PLA/Al2O3 nanoscaffold in different conditions such as concentration, temperature, pH, microwave power and irradiation time. PLA/Al2O3 nanoscaffolds were prepared by a micelle-assisted hydrothermal method. Durability, stability and biodegradable nature of nanopolymers have created the much-applied potential for using this structures in many fields such as dental resin composites. Products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transition electron microscopy (TEM), Fourier transformed infrared spectrum (FT-IR), Dynamic light scattering (DLS) and atomic force microscopy (AFM). The synthesis factors were designed by Taguchi technique to control the process systematically. It was found that the intermolecular crosslinks between PLA and Al2O3 nanoparticles cause significant improves in the mechanical properties of PLA/Al2O3 nanoscaffold as dental nanocomposites. The flexural strength (88.0 MPa), modulus (7.5 GPa) and compressive strength (157.2 MPa) were calculated for PLA/Al2O3 nanoscaffolds loaded in Heliomolar Flow composite resins at 80 ppm (wt) concentration.


Discovery and structure-activity relationship of plastoquinone analogs as anticancer agents against chronic myelogenous leukemia cells.
Two series of amino-1,4-benzoquinones (AQ1-18) based on the structural analogs of plastoquinones were synthesized and the structure-activity relationship against chronic myelogenous leukemia activity was examined. All of the synthesized compounds were tested for their cytotoxic effects on different leukemic cell lines. Of interest, AQ15 exhibited a better selectivity than the reference drug imatinib on cancer cells. Owing to this, AQ15 was selected for a further apoptosis/necrosis evaluation where AQ15-treated K562 cells demonstrated similar apoptotic effects like imatinib-treated cells at their IC50 values. The inhibitory effects of AQ15 and the other three compounds with various activities against eight tyrosine kinases, including ABL1, were investigated. AQ15 showed weak activity against ABL1, and a correlation was observed between the anti-K562 and anti-ABL1 activities. The binding mode of AQ15 into the ATP binding pocket of ABL1 kinase was predicted in silico, showing the formation of some key interactions. In addition, AQ15 was shown to suppress the downstream signaling of BCR-ABL in K562 cells. Finally, AQ15 obviously cleaved DNA in the presence of an iron(II) complex system, indicating that this can be the major mechanism of its antiproliferative action, whereas the mild inhibition of ABL kinase is just in-part mechanism of its overall outstanding cellular activity.


Cardiovascular effects of serotonin agonists and antagonists.
The effects of serotonin (5-hydroxytryptamine; 5-HT) on the cardiovascular system are complex. These effects, consisting of bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction are mediated by three main sets of receptors called 5-HT1-like, 5-HT2, and 5-HT3. In addition, recent findings suggest the participation of a putative 5-HT4 receptor. Though selective 5-HT1A receptor agonists can lower heart rate (and arterial blood pressure), 5-HT usually lowers heart rate by eliciting an initial short-lasting hypotension due to bradycardia (von Bezold-Jarisch-like reflex) via 5-HT3 receptors located on sensory vagal nerve endings in the heart. Once this bradycardia reflex is suppressed--for example, during deep anesthesia, vagotomy, or spinal section--5-HT can increase heart rate in different species by a variety of mechanisms. Myocardial 5-HT1-like, 5-HT2, and 5-HT4 receptors appear to be involved in the cat, rat, and pig, respectively. 5-HT-induced tachycardia in the dog and rabbit is due mainly to release of catecholamines and involves 5-HT2 receptors on the adrenal medulla and 5-HT3 receptors on postganglionic cardiac sympathetic nerve fibers. Recently, 5-HT3 receptors also have been implicated in the 5-HT-induced tachycardia in the conscious dog. The blood pressure response to 5-HT is usually triphasic and consists of a von Bezold-Jarisch-like reflex, a middle pressor phase, and a longer-lasting hypotension. The pressor response is a consequence of vasoconstriction mediated via 5-HT2 receptors; however, vasoconstriction in the dog saphenous vein and cephalic arteries and arteriovenous anastomoses is due to stimulation of 5-HT1-like receptors. The depressor response exclusively involves 5-HT1-like receptors located at four different sites: (a) central nervous system (decrease in sympathetic and increase in vagal nervous activity), (b) sympathetic nerve terminals (reduction of transmitter release), (c) vascular smooth muscle (vasodilatation), and (d) vascular endothelium (release of a relaxant factor, probably nitric oxide). Arteriolar dilatation, together with the constriction of arteriovenous anastomoses, leads to an increase in nutrient (tissue; capillary) blood flow. The 5-HT1-like receptors are heterogeneous in nature; however, apart from the resemblance of the central nervous system 5-HT1-like receptor causing hypotension and bradycardia to the 5-HT1A binding subtype, the relationship of the other 5-HT1-like receptors to 5-HT1 binding subtypes is still debatable.(ABSTRACT TRUNCATED AT 400 WORDS)


Angiotensin mediates stimulation of ventilation after vasopressin V1 receptor blockade.
We tested the hypothesis that respiration would be stimulated after vasopressin (AVP) V1 receptor blockade because of disinhibition and activation of the renin-angiotensin system. Intravenous infusion of angiotensin II (ANG II) stimulates respiration, presumably centrally, via circumventricular organs. In the present study, the AVP V1 receptor antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine]-Arg8-AVP (PMP; 10 micrograms/kg i.v.) was administered to six awake resting dogs. Measurements were made 30 min prior, and 60 min subsequent, to injection of PMP (protocol 1). In three other protocols, the ANG II blocker saralasin (0.5 microgram.kg-1.min-1 i.v.) was infused starting 20 min before PMP (protocol 2) and 30 min after PMP (protocol 4) and saline was infused (0.2 ml/min) over 90 min as a control (protocol 3). After PMP in protocol 1, alveolar ventilation increased and arterial PCO2 decreased (approximately 3 Torr). ANG II receptor blockade prevented (protocol 2) and reversed (protocol 4) respiratory stimulation by PMP. Despite ventilatory stimulation, plasma renin activity and ANG II were not increased after PMP relative to control (protocol 3). We conclude that AVP acts at V1 receptors to inhibit formation of brain ANG II. Brain ANG II must modulate respiratory control via a circumventricular organ, because systemically administered saralasin, which does not cross the blood-brain barrier, blocked stimulation of respiration.


Palpebral dimensions in Brazilian children: assessment based on digital images.
To determine palpebral dimensions and development in Brazilian children using digital images. An observational study was performed measuring eyelid angles, palpebral fissure area and interpupillary distance in 220 children aged from 4 to 72 months. Digital images were obtained with a Sony Lithium movie camera (Sony DCR-TRV110, Brazil) in frontal view from awake children in primary ocular position; the object of observation was located at pupil height. The images were saved to tape, transferred to a Macintosh G4 (Apple Computer Inc., USA) computer and processed using NIH 1.58 software (NTIS, 5285 Port Royal Rd., Springfield, VA 22161, USA). Data were submitted to statistical analysis. All parameters studied increased with age. The outer palpebral angle was greater than the inner, and palpebral fissure and angles showed greater changes between 4 and 5 months old and at around 24 to 36 months. There are significant variations in palpebral dimensions in children under 72 months old, especially around 24 to 36 months.


Research Methods and New Advances in Drug-Drug Interactions Mediated by Renal Transporters.
The kidney is critical in the human body's excretion of drugs and their metabolites. Renal transporters participate in actively secreting substances from the proximal tubular cells and reabsorbing them in the distal renal tubules. They can affect the clearance rates (CLr) of drugs and their metabolites, eventually influence the clinical efficiency and side effects of drugs, and may produce drug-drug interactions (DDIs) of clinical significance. Renal transporters and renal transporter-mediated DDIs have also been studied by many researchers. In this article, the main types of in vitro research models used for the study of renal transporter-mediated DDIs are membrane-based assays, cell-based assays, and the renal slice uptake model. In vivo research models include animal experiments, gene knockout animal models, positron emission tomography (PET) technology, and studies on human beings. In addition, in vitro-in vivo extrapolation (IVIVE), ex vivo kidney perfusion (EVKP) models, and, more recently, biomarker methods and in silico models are included. This article reviews the traditional research methods of renal transporter-mediated DDIs, updates the recent progress in the development of the methods, and then classifies and summarizes the advantages and disadvantages of each method. Through the sorting work conducted in this paper, it will be convenient for researchers at different learning stages to choose the best method for their own research based on their own subject's situation when they are going to study DDIs mediated by renal transporters.


A molecular dynamics study of lithium-containing aprotic heterocyclic ionic liquid electrolytes.
Classical molecular dynamics simulations were performed on twelve different ionic liquids containing aprotic heterocyclic anions doped with Li+. These ionic liquids have been shown to be promising electrolytes for lithium ion batteries. Self-diffusivities, lithium transference numbers, densities, and free volumes were computed as a function of lithium concentration. The dynamics and free volume decreased with increasing lithium concentration, and the trends were rationalized by examining the changes to the liquid structure. Of those examined in the present work, it was found that (methyloxymethyl)triethylphosphonium triazolide ionic liquids have the overall best performance.


A nomogram for predicting the probability of recurrence in patients with carcinomas located in the ampulla of Vater.
Background and Objectives: The standard treatment for carcinomas of the ampulla of Vater (CAV) is surgical resection. Nevertheless, recurrence is observed in half of the patients within five years after cancer surgery. In this study, we aimed to identify predictive factors and develop a nomogram capable of predicting the risk of recurrence in post-resection CAV patients. Methods: Our study cohort was composed of two hundred and twelve patients who had undergone radical surgery for CAV between 2000 and 2012. Clinicopathological variables predictive of recurrence were identified using univariate analysis. A Cox proportional hazards model was used to select the predictive factors used for the nomogram. Results: The 5-year overall survival, cancer-specific survival and disease-free survival rates were 44.3%, 51.1%, and 42.8%, respectively. The five most predictive variables for tumor recurrence were chosen to develop the nomogram. The nomogram had a highly predictive performance, with a bootstrap-corrected concordance index of 0.72 (95% confidence interval, 0.67-0.79). Furthermore, the performance of the nomogram was found to be better than the American Joint Committee on Cancer (AJCC) staging system due to better homogeneity, higher ability of discrimination and higher risk stratification of the model. Conclusions: We developed a predictive nomogram for estimating tumor relapse probability in CAV patients after radical surgery. This nomogram might be more informative than the AJCC staging system and may allow for better estimation of the probability of relapse after surgical resections.


PIDD1 in cell cycle control, sterile inflammation and cell death.
The death fold domain-containing protein PIDD1 has recently attracted renewed attention as a regulator of the orphan cell death-related protease, Caspase-2. Caspase-2 can activate p53 to promote cell cycle arrest in response to centrosome aberrations, and its activation requires formation of the PIDDosome multi-protein complex containing multimers of PIDD1 and the adapter RAIDD/CRADD at its core. However, PIDD1 appears to be able to engage with multiple client proteins to promote an even broader range of biological responses, such as NF-κB activation, translesion DNA synthesis or cell death. PIDD1 shows features of inteins, a class of self-cleaving proteins, to create different polypeptides from a common precursor protein that allow it to serve these diverse functions. This review summarizes structural information and molecular features as well as recent experimental advances that highlight the potential pathophysiological roles of this unique death fold protein to highlight its drug-target potential.


Bioactive substances from insect pathogenic fungi.
Insect pathogenic fungi have opened up a relatively untapped area of natural product research which, unfortunately, has not received much attention to date. Found in wild abundance in wet tropical Thailand, the insect fungi are shown to contribute not only as controllers of insect populations but also as rich sources of structurally novel biologically active substances.


Age-associated impairments in tissue strength and immune response in a rat vaginal injury model.
Surgical repair of pelvic organ prolapse often includes native tissue repair during which the patient's own vaginal connective tissue is used to achieve pelvic support. This method, based on plication and suspension often yields suboptimal anatomical outcomes, possibly due to inadequate healing of the vaginal connective tissue. We hypothesized that age might have a negative effect on the time course and tissue biomechanics of vaginal wound healing in a rat model. Fifty young (12 weeks) and old (12 months) female 344BN Fischer rats were subjected to a posterior midline vaginal incision. The time course of repair was determined by measuring the size of the wound on days 1, 3, 7, and 14 post-injury. These findings correlated with the immune response to injury using a marker of impaired wound healing, the inflammatory cytokine macrophage migration inhibitory factor in the vaginal muscularis. Biomechanical properties of the healed vaginal tissue were tested 30 days post-injury. Wound healing was assessed on days 1, 3, 7, and 14 post-injury. On day 3 post-injury, the wounds in the young animals had all closed whereas the wounds in the old animals remained open. Furthermore, on day 7, the wound gap was still filled with granulation tissue in the old rats, whereas for the young rats, the wound area was almost indistinguishable from the non-injured area. Macrophage migration inhibitory factor was highly expressed in the vaginal epithelium and in the vaginal muscularis after injury. When compared with young animals, macrophage migration inhibitory factor levels of old rats began to rise more than 2 days later and the increased tissue expression persisted for 7 days longer. The breakpoint force of the healed vagina of old rats was almost 4-fold weaker than in young rats. At 30 days post-injury, the healed vagina in old rats regained less of the original (healthy) force at breakpoint than the young rats. In this rat model, age impaired vaginal wound healing, which was reflected in the altered inflammatory response to injury and reduced tissue strength.


A reaction-diffusion system modeling the spread of resistance to an antimalarial drug.
A mathematical model representing the difusion of resistance to an antimalarial drug is developed. Resistance can spread only when the basic reproduction number of the resistant parasites is bigger than the basic reproduction number of the sensitive parasites (which depends on the fraction of infected people treated with the antimalarial drug). Based on a linearization study and on numerical simulations, an expression for the speed at which resistance spreads is conjectured. It depends on the ratio of the two basic reproduction numbers, on a coefficient representing the difusion of mosquitoes, on the death rate of mosquitoes infected by resistant parasites, and on the recovery rate of nonimmune humans infected by resistant parasites.


Estimating the value of implementing reimbursement decisions: What can payers and manufacturers learn from economics?
Implementation of reimbursement decisions is important to payers and manufacturers, however, evidence shows that it is highly variable. An economic framework is available to assess its value that has been successfully applied and which has developed over time to produce a more realistic representation of the real world. The framework incorporates the value of information, technology diffusion, and the interaction between the two, to generate a value of implementation. While potentially complex to apply, simple analyses are possible and qualitative lessons identified from its associated literature. Six lessons are identified which highlight the importance of considering pricing, population size, technology diffusion, evidence generation, and cost-effectiveness. Consideration of these issues would help payers and manufacturers to work together in a combined effort to increase the implementation of new technologies and generate greater value to society.


Simultaneous amplification and identification of 25 human papillomavirus types with Templex technology.
The majority of existing human papillomavirus (HPV) genotyping assays are based on multiplex PCR using consensus or degenerate primers. We developed a Templex HPV assay that simultaneously detects and identifies 25 common HPV genotypes in a single-tube reaction using type-specific primers for the HPV-specific E6 and E7 genes. The analytical sensitivities of the Templex assay for HPV type 16 (HPV-16), -18, and -56 were 20, 100, and 20 copies per reaction mixture, respectively. The Templex assay provides semiquantitative information on each type when multiple HPV types coexist in one reaction. We tested 109 clinical cervical specimens previously evaluated with the Digene HC2 high-risk HPV DNA test and found 95.4% concordance between the assay results. The Templex assay provided type-specific results and found multiple types in 29.2% (14 of 48) of high-risk HPV-positive samples. The entire Templex procedure, including DNA extraction, can be completed within 5 hours, providing a rapid and reliable diagnostic tool for HPV detection and typing that is amenable to automation.


Structure-based dual affinity optimization of a SARS-CoV-1/2 cross-reactive single-domain antibody.
The SARS coronavirus 2 (SARS-CoV-2) spike (S) protein binding to the human ACE2 receptor is the molecular event that initiates viral entry into host cells and leads to infection and virus replication. There is a need for agents blocking viral entry into host cells that are cross-reactive with emerging virus variants. VHH-72 is an anti-SARS-CoV-1 single-domain antibody that also exhibits cross-specificity with SARS-CoV-2 but with decreased binding affinity. Here we applied a structure-based approach to affinity-mature VHH-72 for the SARS-CoV-2 spike protein while retaining the original affinity for SARS-CoV-1. This was achieved by employing the computational platform ADAPT in a constrained dual-affinity optimization mode as a means of broadening specificity. Select mutants designed by ADAPT were formatted as fusions with a human IgG1-Fc fragment. These mutants demonstrated improved binding to the SARS-CoV-2 spike protein due to decreased dissociation rates. Functional testing for virus neutralization revealed improvements relative to the parental VHH72-Fc up to 10-fold using a SARS-CoV-2 pseudotyped lentivirus and 20-fold against the SARS-CoV-2 authentic live virus (Wuhan variant). Binding and neutralization improvements were maintained for some other SARS-CoV-2 variants currently in circulation. These improved VHH-72 mutants are predicted to establish novel interactions with the S antigen. They will be useful, alone or as fusions with other functional modules, in the global quest for treatments of COVID-19 infections.


Mismatch Repair Protein Msh2 Is Necessary for Macronuclear Stability and Micronuclear Division in Tetrahymena thermophila.
Mismatch repair (MMR) is a conserved mechanism that is primarily responsible for the repair of DNA mismatches during DNA replication. Msh2 forms MutS heterodimer complexes that initiate the MMR in eukaryotes. The function of Msh2 is less clear under different chromatin structures. Tetrahymena thermophila contains a transcriptionally active macronucleus (MAC) and a transcriptionally silent micronucleus (MIC) in the same cytoplasm. Msh2 is localized in the MAC and MIC during vegetative growth. Msh2 is localized in the perinuclear region around the MIC and forms a spindle-like structure as the MIC divides. During the early conjugation stage, Msh2 is localized in the MIC and disappears from the parental MAC. Msh2 is localized in the new MAC and new MIC during the late conjugation stage. Msh2 also forms a spindle-like structure with a meiotic MIC and mitotic gametic nucleus. MSH2 knockdown inhibits the division of MAC and MIC during vegetative growth and affects cellular proliferation. MSH2 knockdown mutants are sensitive to cisplatin treatment. MSH2 knockdown also affects micronuclear meiosis and gametogenesis during sexual development. Furthermore, Msh2 interacts with MMR-dependent and MMR-independent factors. Therefore, Msh2 is necessary for macronuclear stability, as well as micronuclear mitosis and meiosis in Tetrahymena.


Effects of two different continuous passive motion protocols on the functional activities of total knee arthroplasty inpatients.
The aim of this study was to compare the effects of two different continuous passive motion (CPM) application protocols (low- and high-angle) on the early phase functional activities of total knee arthroplasty inpatients. The study included 170 patients who underwent primary TKA. While 84 of the TKA patients underwent low-angle CPM application, 86 of the patients underwent high-angle CPM application. The patients' functional activities were compared using the Iowa Level of Assistance Scale (ILAS), gait speeds using the Iowa Ambulation Velocity Scale (IAVS), knee scores using the Hospital for Special Surgery (HSS) Knee Score, and the duration of hospital stays with the Visual Analog Scale (VAS) preoperatively and on postoperative Day 2, Day 6, and at discharge. It was found that patients in the high-angle group had lower pain levels than did the patients in the low-angle group postsurgery (p<0.05). Patients in the high-angle group achieved their functional activities more independently on postoperative Day 2, Day 6, and at discharge than did the patients in the low-angle group (p<0.05). However, gait speed of patients in the former group was lower than that of the patients in the latter group (p<0.05). Although low-angle CPM application produced better results in terms of gait speed following TKA, the high-angle CPM application was superior in terms of independence levels of functional activities in the early postsurgery period. This result suggests that the appropriate use of rehabilitation methods such as CPM applications may guide clinicians to increase patients' level of independence.


Specialized Pro-Resolving Lipid Mediators: Endogenous Roles and Pharmacological Activities in Infections.
During an infection, inflammation mobilizes immune cells to eliminate the pathogen and protect the host. However, inflammation can be detrimental when exacerbated and/or chronic. The resolution phase of the inflammatory process is actively orchestrated by the specialized pro-resolving lipid mediators (SPMs), generated from omega-3 and -6 polyunsaturated fatty acids (PUFAs) that bind to different G-protein coupled receptors to exert their activity. As immunoresolvents, SPMs regulate the influx of leukocytes to the inflammatory site, reduce cytokine and chemokine levels, promote bacterial clearance, inhibit the export of viral transcripts, enhance efferocytosis, stimulate tissue healing, and lower antibiotic requirements. Metabolomic studies have evaluated SPM levels in patients and animals during infection, and temporal regulation of SPMs seems to be essential to properly coordinate a response against the microorganism. In this review, we summarize the current knowledge on SPM biosynthesis and classifications, endogenous production profiles and their effects in animal models of bacterial, viral and parasitic infections.


Microsurgical Tissue Transfer in Breast Reconstruction.
Autologous breast reconstructions have grown in popularity because of their durability, aesthetic outcomes, symmetry, increase in external beam radiotherapy use, and potential aesthetic enhancement at the donor site. Increasing patient expectations for predictable high aesthetic outcomes with minimal complications or need for further procedures has been met by refinement in the use of flaps. The authors' microsurgical breast reconstruction center aims to provide this while delivering efficient service. The deep inferior epigastric flaps form 85% and transverse upper gracilis and profunda artery perforator flaps account for 10%; lumbar artery perforator flaps are a new addition to the authors' armamentarium.


Older patients' experience of dressing changes on venous leg ulcers: more than just a docile patient.
The aim of this paper was to describe the lived experiences of older patients with venous leg ulcers, during dressing changes as out patients with a focus of their concerns about care interventions. Research on wound care management has focused on treatment of venous leg ulcer, wound assessments and the choice of dressing material. Few studies have focused on the patients' experience of dressing changes. Fifteen older people with verified venous leg ulcers were recruited in a metropolitan area of Sweden. Data were collected with research interviews in the form of dialogue. Data were analysed with an interpretative phenomenological method developed by Benner. Twelve women and three men participated. The themes were: 'being cared for with a skillful touch', 'feelings of belonging, continuity and affinity', and 'being suppressed into a state where one loses control, leading to feelings of discomfort'. The participants' experiences varied. Some were satisfied and felt that there was a mutual understanding between caregivers and patients, while others were dissatisfied and felt objectified. Understanding the patients as human beings and considering illness as lived experience helped the care providers to perform skillful wound care, in an atmosphere of mutual understanding. The patients suffering from venous leg ulcers wanted to feel worthy of wound treatment and to meet skillful, confident and gentle nurses in a sharing atmosphere. Nurses must be perceptive to the individual's bodily experience of the leg ulcer. Wound care requires a multidimensional clinical approach that involves not only medical and technical care strategies of dressings and bandages, but also aspects that concern the situated-based illness experience that persons suffering from leg ulcers may face.


The Role of Deep Learning-Based Echocardiography in the Diagnosis and Evaluation of the Effects of Routine Anti-Heart-Failure Western Medicines in Elderly Patients with Acute Left Heart Failure.
The role of deep learning-based echocardiography in the diagnosis and evaluation of the effects of routine anti-heart-failure Western medicines was investigated in elderly patients with acute left heart failure (ALHF). A total of 80 elderly patients with ALHF admitted to Affiliated Hangzhou First People's Hospital from August 2017 to February 2019 were selected as the research objects, and they were divided randomly into a control group and an observation group, with 40 cases in each group. Then, a deep convolutional neural network (DCNN) algorithm model was established, and image preprocessing was carried out. The binarized threshold segmentation was used for denoising, and the image was for illumination processing to balance the overall brightness of the image and increase the usable data of the model, so as to reduce the interference of subsequent feature extraction. Finally, the detailed module of deep convolutional layer network algorithm was realized. Besides, the patients from the control group were given routine echocardiography, and the observation group underwent echocardiography based on deep learning algorithm. Moreover, the hospitalization status of patients from the two groups was observed and recorded, including mortality rate, rehospitalization rate, average length of hospitalization, and hospitalization expenses. The diagnostic accuracy of the two examination methods was compared, and the electrocardiogram (ECG) and echocardiographic parameters as well as patients' quality of life were recorded in both groups at the basic state and 5 months after drug treatment. After comparison, the rehospitalization rate and mortality rate of the observation group were lower than the rates of the control group, but the diagnostic accuracy was higher than that of the control group. However, the difference between the two groups of patients was not statistically marked (P > 0.05). The length and expenses of hospitalization of the observation group were both less than those of the control group. The specificity, sensitivity, and accuracy of the examination methods in the observation group were higher than those of the control group, and the differences were statistically marked (P < 0.05). There was a statistically great difference between the interventricular delay (IVD) of the echocardiographic parameters of patients from the two groups at the basic state and the left ventricular electromechanical delay (LVEMD) parameter values after 5 months of treatment (P < 0.05), but there was no significant difference in the other parameters. After treatment, the quality of life of patients from the two groups was improved, while the observation group was more marked than the control group (P < 0.05). Echocardiography based on deep learning algorithm had high diagnostic accuracy and could reduce the possibility of cardiovascular events in patients with heart failure, so as to decrease the mortality rate and diagnosis and treatment costs. Moreover, it had an obvious diagnostic effect, which was conducive to the timely detection and treatment of clinical diseases.


Cathepsin Protease Inhibition Reduces Endometriosis Lesion Establishment.
Endometriosis is a gynecologic disease characterized by the ectopic presence of endometrial tissue on organs within the peritoneal cavity, causing debilitating abdominal pain and infertility. Current treatments alleviate moderate pain symptoms associated with the disorder but exhibit limited ability to prevent new or recurring lesion establishment and growth. Retrograde menstruation has been implicated for introducing endometrial tissue into the peritoneal cavity, but molecular mechanisms underlying attachment and invasion are not fully understood. We hypothesize that cysteine cathepsins, a group of powerful extracellular matrix proteases, facilitate endometrial tissue invasion and endometriosis lesion establishment in the peritoneal wall and inhibiting this activity would decrease endometriosis lesion implantation. To test this, we used an immunocompetent endometriosis mouse model and found that endometriotic lesions exhibited a greater than 5-fold increase in active cathepsins compared to tissue from peritoneal wall or eutopic endometrium, with cathepsins L and K specifically implicated. Human endometriosis lesions also exhibited greater cathepsin activity than adjacent peritoneum tissue, supporting the mouse results. Finally, we tested the hypothesis that inhibiting cathepsin activity could block endometriosis lesion attachment and implantation in vivo. Intraperitoneal injection of the broad cysteine cathepsin inhibitor, E-64, significantly reduced the number of attached endometriosis lesions in our murine model compared to vehicle-treated controls demonstrating that cathepsin proteases contribute to endometriosis lesion establishment, and their inhibition may provide a novel, nonhormonal therapy for endometriosis.


[Unusual complications of median nerve neurolysis].
Two cases of acute post-operative compression of the ulnar nerve after, nerve release of the median nerve in the wrist are reported. The ulnar, nerve was free of any lesion on the preoperative clinical or electrical examination, at the elbow or the wrist. Stenosis of this nerve occurred during the month following the median nerve release as confirmed by EMG. The compression was treated by ulnar nerve release. Such a complication, representing 0.2% in a series of 982 cases of carpal tunnel syndrome, has never been mentioned in the literature. The authors suggest an etiopathogenic hypothesis which guides a new surgical approach.


Medium-depth chemical peels in the treatment of acne scars in dark-skinned individuals.
Multiple modalities are available for treating acne scars, one of which is chemical peeling. To evaluate the efficacy of medium-depth peels in the treatment of acne scars. A total of 15 patients (14 women and 1 man) were seen between November 1998 and March 2000. A medium-depth chemical peel was performed. The peel was performed using a combination of Jessner's solution followed by the application of 35% trichloroacetic acid (TCA). The mean age of patients who entered the study was 28 years. A total of 42 peeling sessions were performed: 13 patients had the full three-session regiment, 1 patient had two sessions, and 1 had only one session. Patients in our study had two forms of acne scars, the atrophic saucer or crater-like form and the pitted (ice-pick) form. Improvement occurred in all except one of our patients. Significant improvement (greater than 75% clearance of lesions) occurred in 1 patient (6.6%), moderate improvement (51-75% clearance) in 8 patients (53.3%), mild improvement (26-50% clearance) in 4 patients (26.6%), minimal improvement (1-25% clearance) in 1 patient (6.6%), and no response in 1 patient (6.6%). All patients had different combinations of the above two forms. Four patients (26.6%) had mainly pitted scars and deep atrophic scars. The clinical response in those patients was moderate, mild, minimal, and no response, respectively. The remainder of our patients had mainly atrophic scars of moderate depth. Nine patients (73.4%) suffered from transient postinflammatory hyperpigmentation. In two of them it was preceded by erythema that lasted for more than 1 month. All patients were free of noticeable pigmentation 3 months after the final peel. Patients in whom hyperpigmentation did not develop were of light brown complexion. We conclude that medium-depth chemical peel is a safe and effective method of treating acne scars even in patients with dark complexion.


One-Year Outcomes After Everolimus-Eluting Stents Implantation in Ostial Lesions of Left Anterior Descending Coronary Arteries.
In recent years, stents are increasingly used in variety of coronary lesions. Ostial lesion of left anterior descending coronary artery (LAD) however remains a challenge area because of the invariable involvement of distal left main coronary artery (LMCA). This study was designed to evaluate the clinical and angiographic outcomes of everolimus-eluting stent (EES) implantation for ostial LAD. EESs were implanted in 45 consecutive patients with ostial LAD stenoses. For complete lesion coverage, stent positing was extended into the distal LMCA in 6 patients (13.3%) with intermediated LMCA narrowing. We assess MACE during one-year follow-up. In-hospital success rate was 100%; neither cardiac death nor stent thrombosis in our patients, but two patients had myocardial infarction in non-related coronary artery during follow-up. Two patients had angiographic restenosis and underwent TLR. The cumulative MACE-free survival rate was 95.6% at one year. EES was in ostial LAD lesions with complete lesion coverage achieving high procedural success rate and acceptable clinical outcomes during one-year follow-up period.


Common scaling patterns in intertrade times of U. S. stocks.
We analyze the sequence of time intervals between consecutive stock trades of thirty companies representing eight sectors of the U.S. economy over a period of 4 yrs. For all companies we find that: (i) the probability density function of intertrade times may be fit by a Weibull distribution, (ii) when appropriately rescaled the probability densities of all companies collapse onto a single curve implying a universal functional form, (iii) the intertrade times exhibit power-law correlated behavior within a trading day and a consistently greater degree of correlation over larger time scales, in agreement with the correlation behavior of the absolute price returns for the corresponding company, and (iv) the magnitude series of intertrade time increments is characterized by long-range power-law correlations suggesting the presence of nonlinear features in the trading dynamics, while the sign series is anticorrelated at small scales. Our results suggest that independent of industry sector, market capitalization and average level of trading activity, the series of intertrade times exhibit possibly universal scaling patterns, which may relate to a common mechanism underlying the trading dynamics of diverse companies. Further, our observation of long-range power-law correlations and a parallel with the crossover in the scaling of absolute price returns for each individual stock, support the hypothesis that the dynamics of transaction times may play a role in the process of price formation.


Confirmatory factor analysis of the Computer Understanding and Experience Scale.
The two-factor structure (Technical Competence, General Competence) of the Computer Understanding and Experience Scale was examined through confirmatory factor analysis with a sample of 293 undergraduates from a medium-sized university located in the southern USA. Analysis indicated that the two-factor subscale structure of the Computer Understanding and Experience Scale was supported. The Computer Understanding and Experience Scale's total score is internally consistent (.82) with reliability coefficients for the two subscales of .75 for Technical Competence and .71 for General Competence. The importance of increasing diversity of the sample in subsequent studies is discussed.


A novel clinical immune-related prognostic model predicts the overall survival of mantle cell lymphoma.
The mantle cell lymphoma (MCL) International Prognostic Index (MIPI) and combined MIPI (MIPI-c) are commonly used for risk classification of MCL patients. However, these indexes lack immune-related parameters. The purpose of this study was to develop a novel prognostic model that integrated clinical and immune parameters. A total of 189 patients with newly diagnosed MCL from January 2010 to June 2020 were enrolled in our study. A nomogram and immune-related prognostic index (IRPI) were established to predict the overall survival (OS) of patients according to univariate and multivariate analyses. Discrimination and calibration were used to compare the prognostic performance of the IRPI, MIPI, and MIPI-c. External validation was performed based on validation dataset (n = 150) from two other centers. The results for the training dataset indicated that B symptoms, platelet count, B2M level, CD4+ T-cell count<26.7% and CD8+ T-cell count>44.2% were predictors for OS. All the prognostic factors were integrated into the nomogram. For the overlap of confidence intervals of each variable, we assigned one point for each factor. The IRPI categorized patients into three risk categories: a score of zero indicated low risk, a score of one or two indicated intermediate risk, and a score of ≥3 indicated high risk. The IRPI showed better discrimination and calibration power than the MIPI and MIPI-c in the training dataset and validation dataset. The novel IRPI is a refined risk stratification index and reflects the strong complementary prognostic effects between clinical and immune parameters in MCL.


Modification of a nonlocal electron energy distribution in a bounded plasma.
It is demonstrated experimentally, in a pulsed discharge, that it is possible to modify the "tail" of a nonlocal electron energy distribution (EED) without significantly changing the electron density and temperature (mean energy). The EED tail is modified by changing the potential of a small portion of the plasma boundary and/or by changing the volume creation rate of electrons with energies in the range of the tail of the EED. The discussed effects are a direct result of the nonlocal nature of the EED and have applications to a number of basic research issues associated with discharges under nonequilibrium conditions. As an example, we discuss the possibility of utilizing these methods to measure electron impact excitation cross sections from the metastable states of atoms, which are difficult to measure by other means. The experiments have been conducted in an argon and argon-nitrogen pulsed rf inductively coupled plasma discharge.


Subinhibitory bismuth-thiols reduce virulence of Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a common pathogen in mechanically ventilated patients and produces a wide array of virulence factors. Bismuth-thiols (BTs) are active in vitro against all bacterial lung pathogens, including P. aeruginosa. The objective of these studies was to examine the biochemical and morphologic effects of sublethal BT concentrations on P. aeruginosa and to evaluate virulence in cell culture. Bismuth-dimercaprol, at a fraction of the minimal inhibitory concentration, reduced alginate expression by 67% in P. aeruginosa, whereas subinhibitory bismuth-ethanedithiol (BisEDT) reduced alginate by 92% in P. syringae. BisEDT effects on lipopolysaccharide content and type III secreted cytoxins were examined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Subinhibitory BisEDT reduced cell-associated lipopolysaccharide, and inhibited processing of the secreted cytotoxic protein ExoU. BisEDT-induced outer membrane blebbing and aggregation of cytoplasmic material was noted in electron microscopy. Virulence of P. aeruginosa was assessed by adherence to epithelial cells and sensitivity to serum killing. BisEDT inhibited adherence of P. aeruginosa to 16HBE14o- cells by 28% and to a collagen matrix by 53%. BisEDT-treated bacteria were also 100-fold more sensitive to serum bactericidal activity. In summary, low BT concentrations affect P. aeruginosa in a variety of ways, the combination of which may help prevent or resolve respiratory tract infection.


3-(3-Fluoro-phenyl-sulfin-yl)-2,5,7-trimethyl-1-benzofuran.
In the title compound, C(17)H(15)FO(2)S, the 3-fluoro-phenyl ring makes a dihedral angle of 86.89 (4)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds. The crystal structure also exhibits a slipped π-π inter-action between the furan rings of neighbouring mol-ecules [centroid-centroid distance = 3.719 (2) Å, inter-planar distance = 3.475 (2) Å and slippage = 1.325 Å].


[Pharmacokinetics of ponsinomycin administered in a syrup form in single 400-800 and 1200 mg doses in healthy volunteers].
Ponsinomycin is a new macrolide. Its pharmacokinetics is characterized by an extensive metabolism. Following oral dosing in human, unchanged ponsinomycin is not found in blood, but 3 main metabolites: Mb12, Mb6 and Mb9a can be assayed. Twelve young healthy volunteers received ponsinomycin orally, at doses equal to 400, 800 and 1,200 mg on 3 separate occasions, according to a cross-over design. Metabolites Mb12, Mb6 and Mb9a were measured in plasma by HPLC. The pharmacokinetics of Mb12 was linear in the range of doses administered. A dose-dependent effect leading to a reduction of the apparent elimination rate when dose increased was observed with Mb9a and more importantly with Mb6.


Enhancement of biological effectiveness of carbon-ion beams by applying a longitudinal magnetic field.
Purpose: A magnetic field longitudinal to an ion beam will potentially affect the biological effectiveness of the radiation. The purpose of this study is to experimentally verify the significance of such effects. Methods and materials: Human cancer and normal cell lines were exposed to low (12 keV/μm) and high (50 keV/μm) linear energy transfer (LET) carbon-ion beams under the longitudinal magnetic fields of B// = 0, 0.1, 0.2, 0.3, or 0.6 T generated by a solenoid magnet. The effects of the magnetic fields on the biological effectiveness were evaluated by clonogenic cell survival. Doses that would result in a survival fraction of 10% (D10s) were determined for each cell line and magnetic field. Results: For cancer cells exposed to the low (high)-LET beams, D10 decreased from 5.2 (3.1) Gy at 0 T to 4.3 (2.4) Gy at 0.1 T, while no further decrease in D10 was observed for higher magnetic fields. For normal cells, decreases in D10 of comparable magnitudes were observed by applying the magnetic fields. Conclusions: Significant decreases in D10, i.e. significant enhancements of the biological effectiveness, were observed in both cancer and normal cells by applying longitudinal magnetic fields of B// ≥ 0.1 T. These effects were enhanced with LET. Further studies are required to figure out the mechanism underlying the observed results.


Alkali-promoted CO dissociation on Cu(111) and Ni(111) at room temperature.
The coadsorption of alkalis (K, Na) and CO on Cu(111) was investigated by high-resolution electron energy loss spectroscopy. Measurements performed at room temperature showed that CO adsorption is partially dissociative on a potassium-precovered Cu(111) surface and fully dissociative for Na/Cu(111). Carbon monoxide molecules occupy adsorption sites directly adjacent to those of alkali adatoms, as suggested by the absence of a threshold alkali precoverage for CO dissociation. On the contrary, for alkali+CO/Ni(111) a threshold alkali precoverage for CO dissociation was found to exist.


Multilayer brain networks can identify the epileptogenic zone and seizure dynamics.
Seizure generation, propagation, and termination occur through spatiotemporal brain networks. In this paper, we demonstrate the significance of large-scale brain interactions in high-frequency (80-200Hz) for the identification of the epileptogenic zone (EZ) and seizure evolution. To incorporate the continuity of neural dynamics, here we have modeled brain connectivity constructed from stereoelectroencephalography (SEEG) data during seizures using multilayer networks. After introducing a new measure of brain connectivity for temporal networks, named multilayer eigenvector centrality (mlEVC), we applied a consensus hierarchical clustering on the developed model to identify the EZ as a cluster of nodes with distinctive brain connectivity in the ictal period. Our algorithm could successfully predict electrodes inside the resected volume as EZ for 88% of participants, who all were seizure-free for at least 12 months after surgery. Our findings illustrated significant and unique desynchronization between EZ and the rest of the brain in the early to mid-seizure. We showed that aging and the duration of epilepsy intensify this desynchronization, which can be the outcome of abnormal neuroplasticity. Additionally, we illustrated that seizures evolve with various network topologies, confirming the existence of different epileptogenic networks in each patient. Our findings suggest not only the importance of early intervention in epilepsy but possible factors that correlate with disease severity. Moreover, by analyzing the propagation patterns of different seizures, we demonstrate the necessity of collecting sufficient data for identifying epileptogenic networks.


Extensor retinaculum of the wrist: sonographic characterization and pseudotenosynovitis appearance.
We have found in our practice that the normal extensor retinaculum of the wrist may appear hypoechoic on sonography and, because it is closely applied to the extensor tendons, may simulate tenosynovitis. This study prospectively evaluates the extensor retinaculum in 50 healthy adult volunteers, characterizing its sonographic appearance. The extensor retinaculum has a characteristic appearance on sonography. A hypoechoic appearance from anisotropy should not be confused with tenosynovitis.


Reactivity of an amidinato silylene and germylene toward germanium(ii), tin(ii) and lead(ii) halides.
The coordination chemistry of an amidinato silylene and germylene toward group 14 element(ii) halides is described. The reaction of the amidinato silicon(ii) amide [LSiN(SiMe3)2] (1, L = PhC(NtBu)2) with SnCl2 and PbBr2 afforded the amidinato silylene-dichlorostannylene and -dibromoplumbylene adducts [L{(Me3Si)2N}SiEX2] (E = Sn, X = Cl (2); E = Pb, X = Br (3)), respectively, in which there is a lone pair of electrons on the Sn(ii) and Pb(ii) atoms. X-ray crystallography, NMR spectroscopy and theoretical studies show conclusively that the Si(ii)-E(ii) bonds are donor-acceptor interactions. Similar electronic structures were found in the amidinato germylene-dichlorogermylene and -dichlorostannylene adducts [L{(Me3Si)2N}GeECl2] (E = Ge (5), Sn (6)), which were prepared by treatment of the amidinato germanium(ii) amide [LGeN(SiMe3)2] (4) with GeCl2·dioxane and SnCl2, respectively.


Prefrontal Dopaminergic Mechanisms of Extinction in Adolescence Compared to Adulthood in Rats.
Adolescents with anxiety disorders attain poorer outcomes following extinction-based treatment compared to adults. Extinction deficit during adolescence has been identified to involve immaturity in the medial prefrontal cortex (mPFC). Findings from adult rodents suggest extinction involves dopamine signaling in the mPFC. This system changes dramatically during adolescence, but its role in adolescent extinction is unknown. Therefore, we investigated the role of prefrontal dopamine in extinction using Pavlovian fear conditioning in adolescent and adult rats. Using quantitative PCR (qPCR) analyses, we measured changes in dopamine receptor gene expression in the mPFC before and after extinction. We then enhanced dopamine 1 receptor (D1R) or dopamine 2 receptor (D2R) signaling in the infralimbic cortex (IL) of the mPFC using agonists at the time of extinction. Adolescent rats displayed a deficit in extinction retention compared to adults. Extinction induced a reduction in D1R compared to D2R gene expression in adolescent rats, whereas an increase of D1R compared to D2R gene expression was observed in adult rats. Acutely enhancing IL D1R signaling using SKF-81297 had no effect on extinction at either age. In contrast, acutely enhancing IL D2R signaling with quinpirole significantly enhanced long-term extinction in adolescents, and impaired within-session extinction in adults. Our results suggest a dissociated role for prefrontal dopamine in fear extinction during adolescence compared to adulthood. Findings highlight the dopamine system as a potential pharmacological target to improve extinction-based treatments for adolescents.


Diabetes insipidus and spinal cord injury: a challenging combination.
Diabetes insipidus is a life-threatening condition in which the kidneys excrete huge quantities of diluted urine. Diabetes insipidus as a sequela of head trauma is unusual, but not rare. When it arises in conjunction with a spinal cord injury (SCI), diabetes insipidus not only is life threatening but also raises challenges for bladder retraining. This article describes the pathogenesis, diagnosis, and management of diabetes insipidus. A case study is used to demonstrate the patient course and nursing implications, with emphasis on two nursing diagnoses: fluid volume deficit and alterations in urinary elimination.


Network analysis of physical activity and depressive and affective symptoms during COVID-19 home confinement.
The aim of this study was to analyze the network structure of physical activity, frequency, depressive, and affective symptoms in people under home isolation due to COVID-19. A longitudinal study was conducted in two phases (beginning (March 19, 2020) and end of home confinement (April 8, 2020)). The sample consisted of 579 participants from Spain (250 men and 329 women) aged 16 to 92 years (overall sample: M = 47.06, SD = 14.52). A network analysis was performed. Four clusters emerged (PA, depressive symptoms, positive affect, and negative affect). A higher frequency of physical activity was related to better-sustained attention, increased alertness, and enthusiasm. In addition, feelings of guilt and shame were mitigated, and confinement distress and irritability were reduced. Physical activity also mitigated fatigue in women, whereas feelings of unhappiness were reduced in men. Physical activity seems to be an effective option for mitigating the negative effects of the COVID-19 pandemic. Public health policymakers should develop programs to promote physical activity in order to be able to cope with confinement or similar scenarios in the future.


Pregnancy and vaccines.
Vaccination during pregnancy is important for both women and their offspring; however, vaccination rates can be improved, and health care providers are in a unique position to be able to do so. This article summarizes current information on vaccinations and strategies for addressing patients' concerns related to immunization during pregnancy. Particular attention is given to influenza and tetanus, diphtheria and pertussis vaccinations.


Mutations in the R2 subunit of ribonucleotide reductase that confer resistance to hydroxyurea.
Ribonucleotide reductase is an essential enzyme that catalyzes the reduction of ribonucleotides to deoxyribonucleotides for use in DNA synthesis. Ribonucleotide reductase from Escherichia coli consists of two subunits, R1 and R2. The R2 subunit contains an unusually stable radical at tyrosine 122 that participates in catalysis. Buried deep within a hydrophobic pocket, the radical is inaccessible to solvent although subject to inactivation by radical scavengers. One such scavenger, hydroxyurea, is a highly specific inhibitor of ribonucleotide reductase and therefore of DNA synthesis; thus it is an important anticancer and antiviral agent. The mechanism of radical access remains to be established; however, small molecules may be able to access Tyr-122 directly via channels from the surface of the protein. We used random oligonucleotide mutagenesis to create a library of 200,000 R2 mutants containing random substitutions at five contiguous residues (Ile-74, Ser-75, Asn-76, Leu-77, Lys-78) that partially comprise one side of a channel where Tyr-122 is visible from the protein surface. We subjected this library to increasing concentrations of hydroxyurea and identified mutants that enhance survival more than 1000-fold over wild-type R2 at high drug concentrations. Repetitive selections yielded S75T as the predominant R2 mutant in our library. Purified S75TR2 exhibits a radical half-life that is 50% greater than wild-type R2 in the presence of hydroxyurea. These data represent the first demonstration of R2 protein mutants in E. coli that are highly resistant to hydroxyurea; elucidation of their mechanism of resistance may provide valuable insight into the development of more effective inhibitors.


The Antioxidant and Anti-Complementary Activities of Crude Polysaccharides from Trifoliate Orange (Poncirus trifoliate) Seeds.
In this study, I extracted the crude polysaccharides from trifoliate orange (Poncirus trifoliate) seeds, known as TSCP, using water extraction and ethanol precipitation. The monosaccharide composition of TSCP was in the following order: arabinose (28.28 mol%)> galactose (16.76 mol%)> galacturonic acid+glucuronic acid (13.6 mol%)> glucose (12.45 mol%)> rhamnose (4.18 mol%)> mannose (0.57 mol%)> fucose (0.32 mol%). Its total polyphenol contents were 28.66 and 70.96 μg/mL at 1 and 10 mg/mL, respectively (P<0.01). Further, the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity of 10 mg/mL TSCP (31.67%) was higher than that of 1 mg/mL TSCP (8.07%; P<0.01) and also higher than its 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (11.97%) at the same concentration (10 mg/mL; P<0.01). The anti-complementary property of TSCP increased in a concentration-dependent manner (P<0.001), and at 1,000 μg/mL, it was comparable (61.36%) to the positive control (60%) consisting of polysaccharide-K. In conclusion, TSCP might be a potential immune modulator.


Incidence of childhood cancers in rural areas of the Lublin Region in 1988-2000.
The purpose of the work was the analysis of the number and structure of new neoplasm and morbidity in children living in rural areas of the Lublin Region of Poland. the study included the population of children aged 0-17 in the years 1988-2000. The tumours were divided according to the International Classification of Childhood Cancers. The analysis determined the incidence of all tumours and individual types and the rates of percentage structure and incidence. These parameters were calculated for the whole population according to sex and age. 430 cases of childhood cancers were reported. Boys were 53.7%. The most frequent was leukemia (24.4%), neoplasm of CNS (19.5%) and lymphomas (16%). The mean morbidity rate was 100,8 per million (among boys--105.6, girls--95.8). I. The patient's place of residence is one of the factors affecting the structure of cancers. 2. Higher percentage of lymphomas and CNS tumours and lower percentage of leucaemias and tumours of the sympathetic nervous system and bones was observed in the Lublin Region compared to the values determined for the whole country. 3. The population examined showed lower malignant tumour incidence than that in the whole country as well as increased lymphoma incidence.


Heart damage associated with intracranial lesions.
Focal myocytolysis, a form of myocardial damage, has been found to occur in about 8% of patients dying of intracranial lesions. Electrocardiographic abnormalities in patients with brain damage may be due to this. The cause of focal myocytolysis remains unknown, but if it could be prevented it might avert the patient's death from cardiac arrest or arrhythmia. Moreover, more than a minimal degree of this type of damage to the heart might make it unsuitable for transplantation.


Sensitivity of Colletotrichum nymphaeae to Six Fungicides and Characterization of Fludioxonil-Resistant Isolates in China.
Colletotrichum nymphaeae is the dominant species causing anthracnose disease of peach in China. In this study, 140 isolates of C. nymphaeae were assessed for their sensitivity to six fungicides. It was found that C. nymphaeae was highly resistant to carbendazim, procymidone, and boscalid but sensitive to pyraclostrobin and prochloraz. For fludioxonil, the fungus exhibited differential sensitivities (i.e., approximately 14% of isolates were resistant to fludioxonil and the resistance was stable). Fludioxonil-resistant isolates had a mean EC50 value of 2.2380 µg/ml, whereas the mean EC50 value was 0.0194 µg/ml in fludioxonil-sensitive isolates. The mean EC50 values of C. nymphaeae for pyraclostrobin and prochloraz were 0.0083 µg/ml and 0.002 µg/ml, respectively. No cross-resistance was observed between fungicides from different groups. Mycelial growth rate, control efficacy, and osmotic stress responses were significantly different (P < 0.05) between fludioxonil-sensitive (FluS) and -resistant (FluR) isolates, but no significant difference was observed (P > 0.05) in virulence and sporulation between FluS and FluR isolates. No mutation was detected in coding regions of the CnOs-1, Cal, Hk1, Hog1, TPI, and Mrr1 genes. Interestingly, with fludioxonil treatment, the expression of ABC transporter gene atrB was significantly overexpressed in some resistant isolates. However, overexpression of the atrB gene was not detected in one moderately and one highly resistant isolate, indicating that other unknown mechanisms may be involved. Current findings uncovered several effective chemicals and provided the foundation for designing management strategies to practically control peach anthracnose with the most effective demethylation inhibitor fungicides and quinone outside inhibitor fungicides.


SLC38A9: A lysosomal amino acid transporter at the core of the amino acid-sensing machinery that controls MTORC1.
The mechanistic target of rapamycin (serine/threonine kinase) complex 1 (MTORC1) acts as a crucial regulator of cellular metabolism by integrating growth factor presence, energy and nutrient availability to coordinate anabolic and catabolic processes, and controls cell growth and proliferation. Amino acids are critical for MTORC1 activation, but the molecular mechanisms involved in sensing their presence are just beginning to be understood. We recently reported that the previously uncharacterized amino acid transporter SLC38A9 is a member of the lysosomal sensing machinery that signals amino acid availability to MTORC1. SLC38A9 is the first component of this complex shown to physically engage amino acids, suggesting a role at the core of the amino acid-sensing mechanism.


Risk of stomach cancer in patients with gastric or duodenal ulcer.
It has been suggested that the risk of stomach cancer is increased when there is a history of gastric ulcer, but decreased in those with a history of duodenal ulcer. To provide further information on the issue, data from a case-control study of gastric cancer conducted in greater Milan, northern Italy, between 1985 and 1993, were examined. There were 746 cases of gastric cancer below the age of 75 and 2,053 controls admitted to hospital for acute, non-neoplastic, non-hormone-related diseases. A total of 76 (10.2%) cases and 84 (4.1%) controls reported a history of gastric ulcer, corresponding to a multivariate odds ratio (OR) of 2.6 (95% confidence interval, CI = 1.8-3.6). Fifty nine cases (7.9%) and 111 (5.4%) controls reported a history of duodenal ulcer, corresponding to an OR of 1.3 (95% CI = 0.9-1.8). The OR of gastric cancer was significantly above unity for the first five years after diagnosis of gastric ulcer (OR = 7.4, 95% CI 3.7-14.8), and declined thereafter. No consistent pattern of risks was observed after duodenal ulcer. The present data therefore confirm that the risk of gastric cancer is increased after gastric ulcer. They do not support, however, a reduced risk after duodenal ulcer. This may be due to variable baseline characteristics of the populations studied, or to the different role and impact of Helicobacter pylori and other determinants of duodenal ulcer and gastric cancer in various countries.


Hxk2 regulates the phosphorylation state of Mig1 and therefore its nucleocytoplasmic distribution.
Mig1 and Hxk2 are two major mediators of glucose repression in Saccharomyces cerevisiae. However, the mechanism by which Hxk2 participates in the glucose repression signaling pathway is not completely understood. Recently, it has been demonstrated that Hxk2 interacts with Mig1 to generate a repressor complex located in the nucleus of S. cerevisiae. However, the mechanism by which Mig1 favors the presence of Hxk2 in the nucleus is not clear, and the function of Hxk2 at the nuclear repressor complex level is still unknown. Here, we report that serine 311 of Mig1 is a critical residue for interaction with Hxk2 and that this interaction is regulated by glucose. Our findings suggest that Snf1 interacts constitutively with the Hxk2 component of the repressor complex at high and low glucose conditions. Furthermore, we show that Snf1 binds to Mig1 under low glucose conditions and that binding is largely abolished after a shift to high glucose medium. We found that phosphorylation of serine 311 of Mig1 by Snf1 kinase is essential for Mig1 protein nuclear export and derepression of the SUC2 gene in glucose-limited cells. These results allow postulating that the Hxk2 operates by interacting both with Mig1 and Snf1 to inhibit the Mig1 phosphorylation at serine 311 during high glucose grown.


The rgl-1 is a legitimate homologue of lethal giant larvae recessive oncogene in rat.
We have cloned a rat homologue of the Drosophila recessive oncogene lethal (2) giant larvae from rat brain by RT-PCR using primers prepared from sequences conserved amongst lgl family genes. Sequence analysis predicts that the rat rgl-1 gene encodes a 1,036 amino acid polypeptide with a molecular weight of approximately 112 kDa, which contains a domain characteristic of WD-40 proteins. Northern blot analysis revealed that the highest expression of rgl-1 is detected in the testis, with moderate expression in ovary, brain, spleen, and kidney. Since there is a high degree of amino acid similarity among lgl proteins in various species, it is likely that there is an evolutionary relationship among these proteins. The amino acid identity of rgl-1 to Drosophila l(2)gl and mouse mgl-1 proteins showed 30.6 and 96.8%, respectively. The rat tomosyn, previously known as a homologue of Drosophila l(2)gl, showed much lower amino acid identity to Drosophila l(2)gl and mouse mgl-1 proteins (17.8 and 20%, respectively). Functional analysis showed that the expression of a rat rgl-1 cDNA in Saccharomyces cerevisiae missing sop genes, the yeast homologues of the Drosophila l(2)gl, restored partially the Na+ tolerance of the cell. Taken together, these results indicate that rgl-1, not tomosyn, is the legitimate homologue of lgl gene.


Preoperative gluteus medius muscle atrophy as a predictor of walking ability after total hip arthroplasty.
To elucidate the relation between certain preoperative physical parameters and walking with a limp after total hip arthroplasty (THA) and determine whether it is possible to predict the walking ability of patients 6 months after THA. The subjects of this study comprised 74 female patients who had undergone unilateral THA. Before surgery, the hip abductor and knee extensor strengths were measured, the cross-sectional areas (CSAs) of the gluteus medius and rectus abdominis muscles were measured, and the Timed Up and Go test was conducted. The patients were then divided into two groups according to gait observation results 6 months postoperatively: walking without a limp (n=37) and walking with a limp (n=37). The discriminating criteria between the two groups were age (61 years), CSA of the gluteus medius muscle (2000 mm2), and CSA of the rectus abdominis muscle (340 mm2). In the multiple logistic regression analysis, the gluteus medius muscle was the only significant predictor of limping after THA (β=1.64, R2=0.19, p<0.01). The results of the present study suggest that preoperative atrophy of the gluteus medius is an useful indicator for predicting walking with a limp 6 months postoperatively.


Microwave-assisted Olefin Metathesis as Pivotal Step in the Synthesis of Bioactive Compounds.
Over the last two decades, olefin metathesis has emerged as a new avenue in the design of new routes for the synthesis of natural products and active pharmaceutical ingredients. In many cases, syntheses based on olefin metathesis strategies provide significant routes in terms of increasing the overall yields, improving the synthesis scope, and decreasing the number of steps. On the other hand, over the last decade, microwave-assisted chemistry has experienced an incredible development, which rapidly opened new areas in organic synthesis and in homogeneous catalysis. In this review article, we highlight applications of microwaveheated olefin metathesis reactions as pivotal steps in the total synthesis of biologically active compounds. By drawing selected examples from the recent literature, we aim to illustrate the great synthetic power and variety of metathesis reactions, as well as the beneficial effects of microwave irradiation over conventional heating sources. The majority of the selected applications of microwave-assisted olefin metathesis cover the synthesis of medium-ring cycles, macrocycles, and peptidomimetics by means of ring-closing metathesis (RCM) and crossmetathesis (CM) routes.


Monochromator-interferometer combination for submillimeter astronomical spectrometry from aircraft.
A simple interferometer placed in front of a liquid helium cooled grating instrument was constructed; we have attained a spectral resolution of ?0.1 cm(-1) in the wavelength range of ~64 cm(-1) (157 microm) during observations from the NASA Kuiper Airborne Observatory. Spectra obtained on the planetary nebula NGC 7027 are shown.


Racial patterns of alcoholic beverage use.
Among 59,766 persons who had routine health examinations in the years 1978 through 1980, the proportions reporting drinking among self-classified racial groups were: white, 89.5%; Latin, 84.8%; Japanese, 81.9%; black, 79.8%; Chinese, 68.1%; Filipino, 63.9%. Reported use of 3 or more drinks daily was similar in whites, Latins, and blacks but was much lower in the Asian groups. Men of all races reported more drinking than women. A large proportion of drinkers in all race-sex subgroups reported use of small amounts of alcohol, and most nondrinkers reported lifelong abstinence. Wine drinking (2+ days/week) was favored over spirits or beer by whites of both sexes and women of most races; beer use was favored by men of all races except white. All race-sex groups reported a strong alcohol-cigarette smoking association. Comparison with data collected 15 years earlier showed a substantial decline in reported proportions of abstainers and heavier (3+) drinkers as well as apparent narrowing of race-sex differences.


Fluorescence- and Radiolabeling of [Lys4,Nle17,30]hPP Yields Molecular Tools for the NPY Y4 Receptor.
The neuropeptide Y (NPY) Y4 receptor (Y4R) is involved in energy homeostasis and considered a potential drug target for the treatment of obesity. Only a few molecular tools, i.e., radiolabeled and fluorescent ligands, for the investigation of the Y4R were reported. Previously, [Lys4]hPP proved to be an appropriate full-length PP analog to prepare a fluorescent ligand by derivatization at the ε-amino group. To preclude oxidation upon long-term storage, we replaced the two methionine residues in [Lys4]hPP by norleucine and prepared the corresponding [3H]propionylated ([3H]12) and cyanine labeled (13) peptides, which were characterized and compared with a set of reference compounds in binding (Y1, Y2, Y4, and Y5 receptors) and functional (luciferase gene reporter, beta-arrestin-1,2) Y4R assays. Both molecular probes proved to be useful in radiochemical and flow cytometric saturation and competition Y4R binding experiments. Most strikingly, there was a different influence of the composition of buffer on equilibrium binding and kinetics: [3H]12 affinity (Kd in Na+-free buffer: 1.1 nM) clearly decreased with increasing sodium ion concentration, whereas dissociation and Y4R-mediated internalization of 13 (Kd in Na+-free buffer: 10.8 nM) were strongly affected by the osmolarity of the buffer as demonstrated by confocal microscopy. Displacement of [3H]12 and 13 revealed a tendency to higher apparent affinities for a set of reference peptides in hypotonic (Na+-free) compared to isotonic buffers. The differences were negligible in the case of hPP but up to 270-fold in the case of GW1229 (GR231118). By contrast, no relevant influence of Na+ on Y5R affinity became obvious, when the radioligands [H]12 and [3H]propionyl-pNPY were investigated in saturation binding and competition binding.


Antimicrobial resistance and putative virulence genes of Pseudomonas aeruginosa isolates from patients with respiratory tract infection.
Pseudomonas aeruginosa is a common agent causing community acquired and nosocomial respiratory tract infections, with particularly life-threatening manifestations in patients who are immunocompromised of who have cystic fibrosis. This study investigated the occurrence of extended-spectrum β-lactamases (ESBLs) and metallo β-lactamase (MBL) in association with important putative virulence genes and genotypes variation among P. aeruginosa isolates from respiratory tract infection of Jordanian patients. Over a period of 8-month, a total of 284 respiratory tract samples were obtained from patients diagnosed with respiratory tract infection while attending the Pulmonary Clinic/Intensive Care Unit, Jordan University Hospital (JUH). At the time of sampling most were inpatients (86.9%). Samples were cultured specifically for P. aeruginosa. A total of 61/284 (21.5%) P. aeruginosa isolates were recovered from respiratory samples of patients. The percentage of MDR P. aeruginosa isolates was 52.5%, and all isolates were susceptible to colistin with lower rates of susceptibility to other tested antibiotics. Positive genes of blaCTX-M, blaVEB, blaTEM, blaGES and blaSHV were detected in 68.9%, 18.9%, 18.9%, 15.6% and 12.5% of isolates, respectively. Genotyping revealed no significant genetic relationship among MDR P. aeruginosa isolates from hospitalized patients as judged by the constructed dendrogram and the presence of 14 genotypic groups. The percentages of the virulence genes algD, lasB, toxA, exoS, and exoU among P. aeruginosa isolates were 98%, 98%, 80%, 33% and 33%, respectively, and 87% of isolates produced pyocyanin. The present study demonstrates high occurrence of MDR P. aeruginosa isolates carrying blaCTX-M genes. No specific associations were found between antibiotic resistance, virulence genes and genotypes among MDR isolates.